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Experimental manipulation of population-level MHC diversity controls pathogen virulence evolution in Mus musculus
D H Cornwall1, J L Kubinak2, E Zachary1
1Department of Biology, University of Utah, Salt Lake City, UT, USA.
Journal of Evolutionary Biology
|December 22, 2017
Summary
Host genetic diversity, specifically at the major histocompatibility complex (MHC) loci, naturally limits pathogen virulence. Pathogen adaptation is impeded by exposure to diverse host genotypes, maintaining lower virulence levels in natural systems.
Area of Science:
- Evolutionary biology
- Immunology
- Virology
Background:
- Pathogen virulence can reach higher levels in laboratory settings than observed naturally.
- Host genetic diversity is hypothesized to limit pathogen virulence due to adaptation trade-offs.
Purpose of the Study:
- To investigate the role of host genetic diversity, specifically at the major histocompatibility complex (MHC), in limiting pathogen virulence.
- To test the hypothesis that MHC diversity impedes pathogen adaptation and virulence.
Main Methods:
- Serial passage of Friend virus complex (FVC) through two rounds.
- Comparison of FVC passage in hosts with identical MHC genotypes (pure passage) versus diverse MHC genotypes (alternated passage).
Main Results:
- Alternated passages resulted in a significant reduction in viral titre (31%) and virulence (54%) compared to pure passages.
- MHC diversity impeded FVC adaptation, leading to reduced virulence, even when initially encountering a resistant host genotype.
Conclusions:
- Genetic variation at MHC loci is crucial for limiting virulence in rapidly evolving pathogens.
- Serial exposure to diverse MHC genotypes acts as an impediment to pathogen adaptation.
- Negative frequency-dependent selection may maintain MHC diversity in host populations.
